Joe Launchbury, Tom Youngs, Mako Vunipola and Freddie Burns have also been promoted to the senior squad after making an impact in England's end-of-year internationals.

Lancaster, who also announced a 32-man squad for the second-string Saxons team, said: "The fact that we have spent significant time deliberating over quite a few players shows how tough the competition is to get into this 65 and the strength in depth that is emerging.

"We have made some changes to both squads and we feel that reflects the players' form during the first half of the season.

"There will undoubtedly be movement between the two squads as we go through the RBS 6 Nations and that was evident in the QBE Internationals, with players in form pushing through such as Freddie Burns, Joe Launchbury, Tom Youngs and Mako Vunipola."

James Haskell of Wasps has replaced Phil Dowson in the back row, while Saracens wing David Strettle comes in for Charlie Sharple.

Launchbury takes the place of Wasps colleague Tom Palmer, with Youngs coming in for injured Bath hooker Rob Webber.

At centre, Lancaster has dropped Anthony Allen and Jordan Turner-Hall for Twelvetrees and his Gloucester teammate Burns.

Clark was selected for last season's Six Nations campaign but he was then sidelined for over eight months after admitting in March to breaking Leicester hooker Rob Hawkins' elbow in the Anglo-Welsh Cup final.

Twelvetrees, meanwhile, has impressed in his first season at Gloucester alongside Burns, who made an eye-catching debut in the 38-21 triumph against New Zealand at Twickenham in the end-of-year internationals.

Burns, Launchbury, Vunipola and Youngs were all classed as injury replacements when they played during that series, but they have now been formally selected.

England begin their Six Nations campaign at home to Scotland on February 2.